A clear consensus does not exist about whether the initial dose of
gemcitabine, an essential anticancer
antimetabolite, should be reduced in patients with
liver dysfunction. Adult patients with biliary tract or
pancreatic cancer were divided into three groups according to whether they had mild, moderate, or severe
liver dysfunction, evaluated on the basis of serum
bilirubin and liver
transaminase levels at baseline. As anticancer treatment,
gemcitabine at a dose of 800 or 1000 mg/m(2) was given as an i.v. infusion once weekly for 3 weeks of a 4-week cycle. The patients were prospectively evaluated for adverse events during the first cycle, and the pharmacokinetics of
gemcitabine and its inactive metabolite, difluorodeoxyuridine, were studied to determine the optimal initial dose of
gemcitabine as monotherapy according to the severity of
liver dysfunction. A total of 15 patients were studied.
Liver dysfunction was mild in one patient, moderate in six, and severe in eight. All 15 patients had been undergoing biliary drainage for
obstructive jaundice when they received
gemcitabine. Grade 3
cholangitis developed in one patient with moderate
liver dysfunction who received
gemcitabine at the dose level of 1000 mg/m(2). No other patients had severe treatment-related adverse events resulting in the omission or discontinuation of
gemcitabine treatment. The plasma concentrations of
gemcitabine and difluorodeoxyuridine were similar among the groups. An initial
dose reduction of
gemcitabine as monotherapy for the treatment of biliary tract or
pancreatic cancers is not necessary for patients with
hyperbilirubinemia, provided that
obstructive jaundice is well managed. (Clinical trial registration no. UMIN000005363.)